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Synthesis 2022; 54(21): 4727-4733
DOI: 10.1055/a-1791-7218
special topic
Asymmetric C–H Functionalization

Rhodium-Catalyzed C–H Activation of Indoles for the Construction of Spiroindole Scaffolds

Huiying Wang
a   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P. R. of China
,
Mengmeng Wang
a   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P. R. of China
,
Biao Ma∗
b   Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, P. R. of China
,
Hui-Xiong Dai∗
a   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P. R. of China
b   Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, P. R. of China
c   School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, P. R. of China
› Author AffiliationsWe gratefully acknowledge the Shanghai Institute of Materia Medica; the Chinese Academy of Sciences; the National Natural Science Foundation of China (22001258 and 21920102003); the Youth Innovation Promotion Association CAS (nos. 2014229 and 2018293); Institutes for Drug Discovery and Development, the Chinese Academy of Sciences (no. CASIMM0120163006); the Science and Technology Commission of Shanghai Municipality (17JC1405000, 21ZR1475400, and 18431907100); the Program of Shanghai Academic Research Leader (19XD1424600); and the China Postdoctoral Science Foundation (2019M662854) for financial support.
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Abstract

Spiroindoles are key scaffolds in a large number of natural products, pharmaceuticals, and agrochemicals. Selective C–H activation has emerged as a powerful synthetic approach to streamline the synthesis of substituted spiroindoles. To date, various 2- and 3-indolyl-tethered aza-spiro-centers have been successfully achieved via C–H activation. However, introduction of spiro-containing systems onto the benzenoid core of indole still remains challenging. Herein, a method of Rh(III)-catalyzed selective C7-H activation/cyclization of indole with maleimide to afford novel spiroindole derivatives is reported, which incorporate both succinimide and spirocycle into indole unit. Gram-scale synthesis demonstrates the utility of this protocol, further modification via click chemistry offered a novel scaffold as a versatile spiro linker.

Key words

indole - C7-H activation - spirocycle - succinimide - Rh-catalyzed

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1791-7218.
  • Supporting Information


Publication History

Received: 25 January 2022

Accepted after revision: 08 March 2022

Accepted Manuscript online:
08 March 2022

Article published online:
20 April 2022

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